Identification of a new spliceogenic variant causing severe primary coenzyme Q deficiency.

BACKGROUND AND AIMS

Primary Coenzyme Q (CoQ) deficiency caused by defects is a clinically heterogeneous mitochondrial condition characterized by reduced levels of CoQ in tissues. Next-generation sequencing has lately boosted the genetic diagnosis of an increasing number of patients. Still, functional validation of new variants of uncertain significance is essential for an adequate diagnosis, proper clinical management, treatment, and genetic counseling.

MATERIALS AND METHODS

Both fibroblasts from a proband with deficiency and a knockout cell model have been characterized by a combination of biochemical and genetic analysis (HPLC lipid analysis, Oxygen consumption, minigene analysis, RNAseq, among others).

RESULTS

Here, we report the case of a subject harboring a new variant of the gene in compound heterozygosis, which shows severe clinical manifestations. We present the molecular characterization of this new pathogenic variant affecting the splicing of .

CONCLUSION

Our results highlight the importance of expanding the genetic analysis beyond the coding sequence to reduce the misdiagnosis of primary CoQ deficiency patients.